The purpose of this project is to continue to assess the neurological status of individuals who have abused cocaine and other drugs over a long period of their lives. The acute neuropsychiatric disorders include seizure, psychosis, subarachnoid hemorrhage, and thromboembolic phenomena. However, there are few studies which used the detailed classical neurological examination in order to classify possible different neurological syndromes that might be associated with the use of drugs of abuse. We have thus started to carry out thorough neurological and neuropsychological examination in subjects who are chronic cocaine or polydrug abusers and who are seronegative for HIV. The results of these examinations continue to show evidence of nystagmus, abnormal eye pursuit, abnormal saccades, decreased reflexes, and increased jaw jerk. Vibration and position senses were also abnormal. The presence of nystagmus and increased jaw jerk in these subjects may be related to cocaine effects on brainstem pathways. The reflex and sensory abnormalities appear to correspond to a bilateral symmetric neuropathy. These results suggest that cocaine may cause deleterious effects on the nervous system by causing constriction of the vasa nervorum which supply the peripheral nervous system. These findings suggest a new line of investigation which will focus on the peripheral effects of this well known vasoconstrictor.